Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.

Other Name: ISIS-FXIRx

Experimental: ISIS-FXIRx Dose 3

Group C: ISIS-FXIRx Dose #3

Drug: ISIS-FXIRx Dose #3

Group C: ISIS-FXIRx dose #3 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.

Other Name: ISIS-FXIRx

Active Comparator: Enoxaparin

Enoxaparin (40mg)

Drug: Enoxaparin

Enoxaparin (40mg) will be administered by subcutaneous injection the evening prior to total knee arthroplasty (optionally), 6 to 8 hours after surgery, followed by daily injections for at least 8 additional days post surgery (a total of at least 9 consecutive days). [Except for Canadian region, in which the subcutaneous injection of enoxaparin the evening prior to total knee arthroplasty is expected, resulting in a total of at least 10 consecutive days of enoxaparin.]

Other Names:

Lovenox

Clexane

Eligibility

Ages Eligible for Study:

18 Years to 80 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Give written informed consent

Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Males must be surgically sterile, abstinent, or if engaged in sexual relations of child-bearing potential, must use contraception

Undergoing elective, primary unilateral total knee arthroplasty

Exclusion Criteria:

Body weight <50 kg

Patients at increased risk of bleeding. History of intracranial or intraocular bleeding. History of gastrointestinal and/or endoscopically verified ulcer disease within the past year.

History of excessive intra- or direct post operative bleeding or a traumatic spinal or epidural anesthesia

Brain, spinal, or ophthalmologic surgery within the past 3 months

History of clinically significant liver disease in the past year

Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values

Urine protein or blood persistently positive by dipstick. In the event of positive test results, eligibility may be confirmed with urine microscopy or 24 hour urine protein measurement as applicable

ALT or AST >1.5 x ULN

Total bilirubin >ULN

Platelet count <150,000 (or history of thrombocytopenia)

Hypersensitivity to enoxaparin

Anticipated concomitant use of anticoagulants/antiplatelet agents or the NSAID nimesulide that may affect study outcome or any other drug influencing coagulation (except low dose aspirin and short acting NSAIDs with a half-life <20 hours) at least 7 days before surgery or during treatment with ISIS Rx.

Anticipated use of indwelling intrathecal or epidural catheters

Anemia at Screening

Have any other conditions which could interfere with the patient participating in or completing the study

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713361